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<ep-patent-document id="EP12819138B1" file="EP12819138NWB1.xml" lang="en" country="EP" doc-number="2787882" kind="B1" date-publ="20200422" status="n" dtd-version="ep-patent-document-v1-5">
<SDOBI lang="en"><B000><eptags><B001EP>ATBECHDEDKESFRGBGRITLILUNLSEMCPTIESILTLVFIROMKCYALTRBGCZEEHUPLSK..HRIS..MTNORS..SM..................</B001EP><B003EP>*</B003EP><B005EP>J</B005EP><B007EP>BDM Ver 1.7.2 (20 November 2019) -  2100000/0</B007EP></eptags></B000><B100><B110>2787882</B110><B120><B121>EUROPEAN PATENT SPECIFICATION</B121></B120><B130>B1</B130><B140><date>20200422</date></B140><B190>EP</B190></B100><B200><B210>12819138.4</B210><B220><date>20121204</date></B220><B240><B241><date>20140709</date></B241><B242><date>20160415</date></B242></B240><B250>en</B250><B251EP>en</B251EP><B260>en</B260></B200><B300><B310>201161568700 P</B310><B320><date>20111209</date></B320><B330><ctry>US</ctry></B330></B300><B400><B405><date>20200422</date><bnum>202017</bnum></B405><B430><date>20141015</date><bnum>201442</bnum></B430><B450><date>20200422</date><bnum>202017</bnum></B450><B452EP><date>20191118</date></B452EP></B400><B500><B510EP><classification-ipcr sequence="1"><text>A61B   5/055       20060101AFI20130628BHEP        </text></classification-ipcr><classification-ipcr sequence="2"><text>G01R  33/483       20060101ALI20130628BHEP        </text></classification-ipcr><classification-ipcr sequence="3"><text>G01R  33/485       20060101ALI20130628BHEP        </text></classification-ipcr><classification-ipcr sequence="4"><text>G01R  33/54        20060101ALI20130628BHEP        </text></classification-ipcr><classification-ipcr sequence="5"><text>G01R  33/56        20060101ALI20130628BHEP        </text></classification-ipcr></B510EP><B540><B541>de</B541><B542>POSITIONIERUNG EINES BESTIMMTEN VOLUMENS FÜR MR-SPEKTROSKOPIE</B542><B541>en</B541><B542>POSITIONING OF A VOLUME OF INTEREST FOR MAGNETIC RESONANCE SPECTROSCOPIC IMAGING</B542><B541>fr</B541><B542>POSITIONNEMENT DE VOLUME D'INTÉRÊT POUR IMAGERIE SPECTROSCOPIQUE PAR RÉSONANCE MAGNÉTIQUE</B542></B540><B560><B561><text>WO-A2-2011/050348</text></B561><B561><text>US-A1- 2004 218 796</text></B561><B562><text>RAKESH SHARMA: "Molecular Imaging by Proton Magnetic Resonance Imaging (MRI) and MR Spectroscopic Imaging (MRSI) in Neurodegeneration", INFORMATICA MEDICA SLOVENICA, vol. 10, no. 1, 30 June 2005 (2005-06-30), pages 35-55, XP055056876,</text></B562><B562><text>PARMESHWAR KHURD ET AL: "Facilitating 3D Spectroscopic Imaging through Automatic Prostate Localization in MR Images Using Random Walker Segmentation Initialized via Boosted Classifiers", 22 September 2011 (2011-09-22), PROSTATE CANCER IMAGING. IMAGE ANALYSIS AND IMAGE-GUIDED INTERVENTIONS, SPRINGER BERLIN HEIDELBERG, BERLIN, HEIDELBERG, PAGE(S) 47 - 56, XP019166350, ISBN: 978-3-642-23943-4 page 47 - page 48, paragraph 1 page 49, paragraph 2 - page 53, paragraph 2 page 54, paragraph 3</text></B562><B562><text>GRAEME F. MASON ET AL: "Evaluation of 31P metabolite differences in human cerebral gray and white matter", MAGNETIC RESONANCE IN MEDICINE, vol. 39, no. 3, 1 March 1998 (1998-03-01), pages 346-353, XP055056879, DOI: 10.1002/mrm.1910390303</text></B562><B562><text>W WEBER-FAHR ET AL: "A Fully Automated Method for Tissue Segmentation and CSF-Correction of Proton MRSI Metabolites Corroborates Abnormal Hippocampal NAA in Schizophrenia", NEUROIMAGE, vol. 16, no. 1, 1 May 2002 (2002-05-01), pages 49-60, XP055056883, ISSN: 1053-8119, DOI: 10.1006/nimg.2002.1057</text></B562><B562><text>GÃRAN STARCK ET AL: "A 1H magnetic resonance spectroscopy study in adults with obsessive compulsive disorder: relationship between metabolite concentrations and symptom severity", JOURNAL OF NEURAL TRANSMISSION ; BASIC NEUROSCIENCES, GENETICS AND IMMUNOLOGY, PARKINSON'S DISEASE AND ALLIED CONDITIONS, ALZHEIMER'S DISEASE AND ADOLESCENT PSYCHIATRY RELATED DISORDERS, BIOLOGICAL PSYCHIATRY, BIOLOGICAL CHILD AND ADOLESCENT PSYCHIAT, vol. 115, no. 7, 5 June 2008 (2008-06-05), pages 1051-1062, XP019633952, ISSN: 1435-1463</text></B562><B562><text>ULRIKE DYDAK ET AL: "In Vivo Measurement of Brain GABA Concentrations by Magnetic Resonance Spectroscopy in Smelters Occupationally Exposed to Manganese", ENVIRONMENTAL HEALTH PERSPECTIVES, vol. 119, no. 2, 28 September 2010 (2010-09-28), pages 219-224, XP055056933, ISSN: 0091-6765, DOI: 10.1289/ehp.1002192</text></B562><B562><text>LYUBOMIR ZAGORCHEV ET AL: "Manual Annotation, 3-D Shape Reconstruction, and Traumatic Brain Injury Analysis", 18 September 2011 (2011-09-18), MULTIMODAL BRAIN IMAGE ANALYSIS, SPRINGER BERLIN HEIDELBERG, BERLIN, HEIDELBERG, PAGE(S) 52 - 59, XP019166793, ISBN: 978-3-642-24445-2 cited in the application the whole document</text></B562><B562><text>LYUBOMIR ZAGORCHEV ET AL: "Evaluation of Traumatic Brain Injury Patients Using a Shape-Constrained Deformable Model", 18 September 2011 (2011-09-18), MULTIMODAL BRAIN IMAGE ANALYSIS, SPRINGER BERLIN HEIDELBERG, BERLIN, HEIDELBERG, PAGE(S) 118 - 125, XP019166782, ISBN: 978-3-642-24445-2 cited in the application the whole document</text></B562></B560></B500><B700><B720><B721><snm>ZAGORCHEV, Lyubomir Georgiev</snm><adr><str>c/o High Tech Campus
Building 44</str><city>NL-5656 AE Eindhoven</city><ctry>NL</ctry></adr></B721><B721><snm>YOUNG, Stewart</snm><adr><str>c/o High Tech Campus
Building 44</str><city>NL-5656 AE Eindhoven</city><ctry>NL</ctry></adr></B721></B720><B730><B731><snm>Koninklijke Philips N.V.</snm><iid>101851185</iid><irf>2011P01864WE</irf><adr><str>High Tech Campus 52</str><city>5656 AG Eindhoven</city><ctry>NL</ctry></adr></B731></B730><B740><B741><snm>Philips Intellectual Property &amp; Standards</snm><iid>101808802</iid><adr><str>High Tech Campus 5</str><city>5656 AE Eindhoven</city><ctry>NL</ctry></adr></B741></B740></B700><B800><B840><ctry>AL</ctry><ctry>AT</ctry><ctry>BE</ctry><ctry>BG</ctry><ctry>CH</ctry><ctry>CY</ctry><ctry>CZ</ctry><ctry>DE</ctry><ctry>DK</ctry><ctry>EE</ctry><ctry>ES</ctry><ctry>FI</ctry><ctry>FR</ctry><ctry>GB</ctry><ctry>GR</ctry><ctry>HR</ctry><ctry>HU</ctry><ctry>IE</ctry><ctry>IS</ctry><ctry>IT</ctry><ctry>LI</ctry><ctry>LT</ctry><ctry>LU</ctry><ctry>LV</ctry><ctry>MC</ctry><ctry>MK</ctry><ctry>MT</ctry><ctry>NL</ctry><ctry>NO</ctry><ctry>PL</ctry><ctry>PT</ctry><ctry>RO</ctry><ctry>RS</ctry><ctry>SE</ctry><ctry>SI</ctry><ctry>SK</ctry><ctry>SM</ctry><ctry>TR</ctry></B840><B860><B861><dnum><anum>IB2012056938</anum></dnum><date>20121204</date></B861><B862>en</B862></B860><B870><B871><dnum><pnum>WO2013084142</pnum></dnum><date>20130613</date><bnum>201324</bnum></B871></B870></B800></SDOBI>
<description id="desc" lang="en"><!-- EPO <DP n="1"> -->
<p id="p0001" num="0001">The following generally relates to Magnetic Resonance Spectroscopic Imaging (MRSI) and more particularly to positioning a volume of interest, such as a voxel, in segmented structure in Magnetic Resonance Imaging (MRI) image data, which localizes the volume of interest for Magnetic Resonance Spectroscopic (MRS) biochemical composition analysis.</p>
<p id="p0002" num="0002">MRS is a non-invasive analytical technique that can be used to determine biochemical composition <i>in-vivo</i> in association with, for example, neurodegenerative disorders such as brain tumors, strokes, seizure disorders, and Alzheimer's disease. With MRS, the MR signal produces a spectrum of resonances that correspond to different molecular arrangements of an isotope being "excited." This signature has been used to determine information about metabolic disorders affecting the brain and to provide information about tumor metabolism.</p>
<p id="p0003" num="0003">MRSI combines MRI and MRS. In this combination, a volume of interest (VOI) is used to spatially localize spectra from which MRS determines the biochemical composition for the VOI. Generally, a single voxel is used to define the VOI, and the accuracy of the position of the voxel affects the outcome of the determination of the biochemical composition. That is, if the voxel is intended to be inside certain structure, then positioning the voxel such that a portion of it is outside the structure will result in a less accurate reading as biochemical composition other than the structure is also captured.</p>
<p id="p0004" num="0004">With current state of the art MRSI, the user, in one instance, manually positions the voxel in the structure. Unfortunately, it can be difficult to manually and accurately position a voxel in the structure, especially for small structures. To complicate matters, the voxel is typically constrained, for practical reasons, to be rectangular, whereas structure tends to be irregular in shape. Again, inaccurate positioning can lead to less accurate or even inaccurate results. In some instances, multiple procedures (e.g., corresponding to different contrast images) are performed to facilitate positioning, which makes the process tedious and time consuming.</p>
<p id="p0005" num="0005">Furthermore, even with larger structures where it is easier to position a voxel in the structure or in instances in which the volume of interest is not entirely in the structure, being able to manually position a voxel at the same position in image data from different<!-- EPO <DP n="2"> --> studies (e.g., an initial study and a follow up study) can be difficult. In this instance, results from two studies performed at two different times may not be able to be used to determine whether a disease has regressed, advanced or stayed the same, as the two voxels may not represent the same portion of the structure of interest.</p>
<p id="p0006" num="0006"><nplcit id="ncit0001" npl-type="s"><text>Rakesh Sharma: "Molecular Imaging by Proton Magnetic Resonance Imaging (MRI) and MR Spectroscopic Imaging (MRSI) in Neurodegeneration ", INFORMATICA MEDICA SLOVENICA, vol. 10, no. 1, 30 June 2005, pages 35-55, XP055056876</text></nplcit>, discloses the use of proton magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopic imaging (MRSI) as integrated method to investigate NAA, creatine and choline changes in brain metabolites in Alzheimer's disease and epilepsy. Multislice H-1 MRSI technique of human brain, without volume preselection is used. Furthermore, MRI segmentation and completely automated spectral curve fitting facilitate quantitative data analysis in Alzheimer's disease and molecular imaging basis of prediction for epilepsy at different locations in the brain. MRI and MRSI integrated method is evaluated to characterize the anatomical and metabolite changes in disease.</p>
<p id="p0007" num="0007">Aspects described herein addresses the above-referenced problems and others.</p>
<p id="p0008" num="0008">In one aspect, a MRSI system according to independent claim 1 is provided, with preferred embodiments defined in dependent claims 2-7 and 14.<!-- EPO <DP n="3"> --></p>
<p id="p0009" num="0009">In another aspect, a method according to independent claim 8 is provided, with preferred embodiments defined in dependent claims 9-13.<!-- EPO <DP n="4"> --></p>
<p id="p0010" num="0010">The invention may take form in various components and arrangements of components, and in various steps and arrangements of steps. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the invention.
<dl id="dl0001" compact="compact">
<dt>FIGURE 1</dt><dd>schematically illustrates an example MRSI system which includes a volume of interest positioner.</dd>
<dt>FIGURE 2</dt><dd>schematically illustrates an example of the volume of interest positioner.</dd>
<dt>FIGURE 3</dt><dd>illustrates an example anatomical model.<!-- EPO <DP n="5"> --></dd>
<dt>FIGURE 4</dt><dd>illustrates an example of a rectangular volume of interest positioned inside a structure segmented in MRI image data.</dd>
<dt>FIGURE 5</dt><dd>illustrates an example of an irregular shaped volume of interest positioned inside a structure segmented in MRI image data.</dd>
<dt>FIGURE 6</dt><dd>schematically illustrates a variation of <figref idref="f0002">FIGURE 2</figref> in which the indicia indicating the segmented structure is also output.</dd>
<dt>FIGURE 7</dt><dd>schematically illustrates a variation of <figref idref="f0002">FIGURE 2</figref> in which the segmented structure is identified prior to image segmentation.</dd>
<dt>FIGURE 8</dt><dd>schematically illustrates a variation of <figref idref="f0002">FIGURE 2</figref> in which the image segmenter and the anatomical model bank are not part of the volume of interest positioner.</dd>
<dt>FIGURE 9</dt><dd>illustrates a method for positioning a volume of interest with respect to structure segmented in MRI image data.</dd>
</dl></p>
<p id="p0011" num="0011">Initially referring to <figref idref="f0001">FIGURE 1</figref>, MRSI system 100 is schematically illustrated. The system 100 includes an MRI scanner 102, a volume of interest positioner 104 and an MRS analyzer 128, which is shown in communication with reference data memory 108 and one or more output devices (output device(s)) 110.</p>
<p id="p0012" num="0012">The MRI scanner 102 includes a main magnet 112, gradient (x, y and/or z) coils 114, and an RF coil 116. The main magnet 112 (which can be a superconducting, resistive, permanent, or other type of magnet) produces a substantially homogeneous, temporally constant main magnetic field B<sub>0</sub> in an examination region 118. The gradient coils 114 generate time varying gradient magnetic fields along the x, y and/or z-axes of the examination region 118.</p>
<p id="p0013" num="0013">The illustrated RF coil 116 includes a transmission portion that transmits a radio frequency signal (e.g., at the Larmor frequency of nuclei of interest such as hydrogen, Helium, etc.) that excites the nuclei of interest in the examination region 118 and a receive portion that receives MR signals emitted by excited nuclei. The transmission and receive portions can alternatively be located in separate coils. An MR reconstructor 120 reconstructs the MR signals and generates MRI image data.</p>
<p id="p0014" num="0014">A subject support 122 supports a subject such as a human or animal patient in the examination region 116. A general purpose computing system serves as an operator console 124 and includes an output device such as a display and an input device such as a keyboard, mouse, and/or the like. Software resident on the console 124 allows the operator to<!-- EPO <DP n="6"> --> interact with the scanner 102, for example, to select an imaging protocol, to initiate scanner, etc.</p>
<p id="p0015" num="0015">A data repository 126 can be used to store the image data generated by the scanner 102 and/or other image data. The illustrated data repository 126 may include one or more of a picture archiving and communication system (PACS), a radiology information system (RIS), a hospital information system (HIS), an electronic medical record (EMR) database, a sever, a computer, and/or other data repository. The data repository 126 can be local to the system 100 or remote from the system 100.</p>
<p id="p0016" num="0016">The volume of interest positioner 104 is configured to automatically position a volume of interest, such as one or more voxels, with respect to structure segmented in MRI image data obtained from the scanner 102, the repository 126 and/or other source. The illustrated volume of interest positioner 104 receives an input signal, which can include indicia indicating an anatomical model of interest, particular segmented structure, a positioning rule of interest, and/or other information. As described in greater detail below, in one instance the volume of interest positioner 104 utilizes this input to accurately and reproducibly position a volume of interest with respect to segmented in the MRI image data for MRS analysis. In one instance, this may allow for fully-automatic and accurate volume of interest positioning, which may simplify MRSI planning and/or decrease overall time relative to manual positioning approaches. It is to be appreciated that the functions of the volume of interest positioner 104 can be implemented via a processor executing one or more computer readable instructions encoded or embedded on computer readable storage medium such as physical memory. Additionally or alternatively, at least one of the one or more computer readable instructions executed by the processor is carried by a carrier wave, a signal, or other non-computer readable storage medium such as a transitory medium.</p>
<p id="p0017" num="0017">The MRS analyzer 128 analyzes the volume of interest. This includes quantifying biochemical composition in the volume of interest with respect to the segmented structure and/or comparing the quantified value and/or a change in the quantified value over time with a predetermined threshold to determine whether a disease has regressed or progressed. The accurate positioning of the volume of interest also allows for accurate and reproducible quantification of biochemical composition, development of biochemical biomarkers from MRI image data for certain diseases as the biochemical composition for a disease will generally be the same across patients, development of a database of reference data based on MRI image data for known "normal" patients and known "diseased" patients, and/or extraction/query of information from a segmentation using the normative dataset. It is<!-- EPO <DP n="7"> --> to be appreciated that the functions of the MRS analyzer 128 can be implemented via a processor executing one or more computer readable instructions encoded or embedded on computer readable storage medium such as physical memory. Additionally or alternatively, at least one of the one or more computer readable instructions executed by the processor is carried by a carrier wave, a signal, or other non-computer readable storage medium such as a transitory medium.</p>
<p id="p0018" num="0018">The reference data memory 108 can be used to store results of MRS analysis, including the quantified biochemical composition information, the change in quantified biochemical composition information, the results of the comparison of the quantified biochemical composition information, the results of the comparison of the change in quantified biochemical composition information, the biochemical biomarkers, the database of normative and abnormal reference data, and/or other information. The output device 110 can be used to visually display, transfer and/or otherwise disseminate the information. The output device 110 may include a display monitor, portable memory, a printer, and/or other output device.</p>
<p id="p0019" num="0019"><figref idref="f0002">FIGURE 2</figref> schematically illustrates an example of the volume of interest positioner 104.</p>
<p id="p0020" num="0020">An image segmenter 202 receives the MRI image data and obtains an anatomical model of interest from an anatomical model bank 204. An example anatomical model of interest 300 is shown in <figref idref="f0002">FIGURE 3</figref>. The illustrated model of interest 300 represents a human brain. However, it is to be understood that the model of interest 300 may represent other anatomy. In addition, there may be more than one brain model, for example, one for infants, one for pediatrics and one for adults. The illustrated model of interest 300 is a surface representation of a shape-constrained deformable brain model.</p>
<p id="p0021" num="0021">Examples of suitable brain models are described in<nplcit id="ncit0002" npl-type="b"><text> L.Zagorchev, A. Goshtasby, K. Paulsen, T. McAllister, S. Young, and J. Weese, Manual annotation, 3-D shape reconstruction, and traumatic brain injury analysis, Int'l Workshop Multimodal Brain Image Analysis (MBIA), Toronto, CA, Sept. 2011</text></nplcit>, and<nplcit id="ncit0003" npl-type="s"><text> L.Zagorchev, C. Meyer, T.Stehle, R.Kneser, S. Young, and J. Weese, Evaluation of Traumatic Brain Injury patients using a shape-constrained deformable model, Int'l Workshop Multimodal Brain Image Analysis (MBIA), Toronto, CA, Sept. 2011</text></nplcit>. Other models are also contemplated herein.</p>
<p id="p0022" num="0022">The image segmenter 202 is configured to segment the anatomy represented in the MRI image data based on the anatomy represented in the model of interest 300. In one non-limiting instance, this includes performing an initial registration between the model of<!-- EPO <DP n="8"> --> interest 300 and the MRI image data, transforming the model of interest 300 to the anatomy in the MRI image data based on a transform (e.g., the Hough transform), performing a parametric adaptation of the model of interest 300 (e.g., pose and/or piecewise), and performing a deformable adaptation of the model 300. Other known techniques can alternatively be used.</p>
<p id="p0023" num="0023">A structure identifier 206 identifies one or more segmented structures of the segmented MRI image data. For example, where the input signal includes information identifying the hippocampus, the structure identifier 206 identifies the segmented hippocampus in the segmented MRI image data.</p>
<p id="p0024" num="0024">A volume of interest generator 208 generates a volume of interest to be positioned with respect to the identified segmented structure. In the illustrated example, the volume of interest generator 208 generates and positions the volume of interest based on one or more positioning rules of a positioning rules bank 210. The particular positioning rule may be determined based on the information in the input signal and/or otherwise.</p>
<p id="p0025" num="0025">One rule may indicate that a rectangular voxel volume of interest be placed completely inside the outer surface boundary of the identified segmented structure. <figref idref="f0003">FIGURE 4</figref> shows the placement of a rectangular voxel 402 completely inside an irregular shaped segmented structure 404. In this example, the segmented structure 404 is represented via a mesh, and the voxel 402 is positioned in the mesh using mesh vertices as anchors. For a rectangular voxel, the vertices include the eight (8) corners, and the volume of interest is placed to satisfy constraints imposed by the locations of the mesh vertices, dependent upon the particular criteria desired by the user, for example, that the voxel is fully contained within the boundaries of the structure of interest.</p>
<p id="p0026" num="0026">Returning to <figref idref="f0002">FIGURE 3</figref>, another rule may indicate that a square voxel volume of interest be placed X% inside and (100-X)% outside of the outer surface boundary of the identified segmented structure. Another rule may indicate that a spherical volume of interest be placed completely outside of the surface boundary of the identified segmented structure, but within a predetermined x,y,z coordinate therefrom.</p>
<p id="p0027" num="0027">Another rule may indicate that an irregular shape volume of interest be placed inside the surface boundary so as to conform to the entire shape of the identified segmented structure or a subportion thereof. Irregular shaped voxels could be defined by masking the volume within a structure of interest. <figref idref="f0003">FIGURE 5</figref> shows the placement of an irregular shaped voxel 502 inside an irregular shaped segmented structure 504.<!-- EPO <DP n="9"> --></p>
<p id="p0028" num="0028">Returning to <figref idref="f0002">FIGURE 3</figref>, another rule may indicate a location within the identified segmented structure to place the volume of interest. For example, a rule may indicate whether the volume of interest is placed at the head, middle and/or tail of the segmented structure (e.g., the hippocampus). Another rule may indicate the positioning of multiple volumes of interest. Other rules are also contemplated herein.</p>
<p id="p0029" num="0029">In one instance, the volume of interest generator 208 can be trained to position the volume of interest. In this instance, a user initially manually positions a volume of interest. The volume of interest generator 208 then can automatically position a subsequent same volume of interest based on the manual placement. The volume of interest generator 208 then can automatically positions a next volume of interest based on one or more of the manual placements and previous automatic placement. This can be repeated one or more times. In addition, the user can modify the position of the volume of interest.</p>
<p id="p0030" num="0030">A data router 212 routes the information in the input signal. For example, information corresponding to the model of interest is routed to the image segmenter 202, information corresponding to the segmented structure is routed to the structure of interest identifier 206, and information corresponding to the positioning rule of interest is routed to the volume of interest generator 208.</p>
<p id="p0031" num="0031">The volume of interest positioner 104 outputs at least a signal indicative of the volume of interest positioned in the segmented structure. As shown in <figref idref="f0001">FIGURE 1</figref>, this signal is provided to the MRS analyzer 128, which can analyze the volume of interest as discussed herein and/or otherwise.</p>
<p id="p0032" num="0032">Variations are contemplated.</p>
<p id="p0033" num="0033"><figref idref="f0004">FIGURE 6</figref> shows a variation in which the date router 212 also routes the indicia indicating the segmented structure to the MRS analyzer 128 (<figref idref="f0001">FIGURE 1</figref>). With this indicia, the MRS analyzer 128 can automatically obtain suitable reference data from the reference data memory 130 (<figref idref="f0001">FIGURE 1</figref>) without user interaction. Such reference data can include, for example, biochemical normative data to compare with the biochemical data or change therein determined from the volume of interest.</p>
<p id="p0034" num="0034"><figref idref="f0004">FIGURE 7</figref> shows a variation in which the structure of interest is first identified, and the image segmenter 202 segments a subset of structure such as only the identified structure from the MRI image data. The volume of interest is then placed with respect to the segmented structure as described herein.<!-- EPO <DP n="10"> --></p>
<p id="p0035" num="0035"><figref idref="f0005">FIGURE 8</figref> shows a variation in which the image segmenter 202 and the anatomical model bank 204 are separate from and not part of the volume of interest positioner 104.</p>
<p id="p0036" num="0036"><figref idref="f0005">FIGURE 9</figref> illustrates a method for positioning a volume of interest in structure of interest in MRI image data.</p>
<p id="p0037" num="0037">It is to be appreciated that the ordering of the acts in the methods described herein is not limiting. As such, other orderings are contemplated herein. In addition, one or more acts may be omitted and/or one or more additional acts may be included.</p>
<p id="p0038" num="0038">At 902, MRI image data is segmented, producing segmented MRI image data in which different anatomical structure represented in the MRI image data is segmented. As discussed herein, this may include using a predefined anatomical model.</p>
<p id="p0039" num="0039">At 904, a segmented structure is identified in the segmented MRI image data. The identified segmented structure is identified based on input including information indicative of particular structure selected by a user.</p>
<p id="p0040" num="0040">At 906, a volume of interest is automatically positioned with respect to the identified segmented MRI image data based on one or more positioning rules. The one or more rules include instructions which allow the volume of interest to be accurately and reproducibly positioned in the same segmented structure in the same and/or different segmented MRI image data.</p>
<p id="p0041" num="0041">At 908, the volume of interest is analyzed to determine a biochemical composition of the tissue represented by volume of interest.</p>
<p id="p0042" num="0042">The above may be implemented via one or more processors executing one or more computer readable instructions encoded or embodied on computer readable storage medium such as physical memory which causes the one or more processors to carry out the various acts and/or other functions and/or acts. Additionally or alternatively, the one or more processors can execute instructions carried by transitory medium such as a signal or carrier wave.</p>
<p id="p0043" num="0043">The invention has been described with reference to the preferred embodiments. Modifications and alterations may occur to others upon reading and understanding the preceding detailed description. It is intended that the invention be constructed as including all such modifications and alterations insofar as they come within the scope of the appended claims.</p>
</description>
<claims id="claims01" lang="en"><!-- EPO <DP n="11"> -->
<claim id="c-en-01-0001" num="0001">
<claim-text>A Magnetic Resonance Spectroscopic Imaging (MRSI) system (100), comprising:
<claim-text>a structure identifier (206) that is configured to identify a predetermined segmented structure in segmented MRI image data;</claim-text>
<claim-text>a positioning rules bank (210) which is configured to store rules for positioning a volume of interest (VOI) with respect to the identified predetermined segmented structure of the segmented MRI image data for a Magnetic Resonance Spectroscopic (MRS) biochemical composition analysis; and</claim-text>
<claim-text>a volume of interest generator (208) that is configured to position the volume of interest with respect to the identified predetermined segmented structure based on one or more of the rules for positioning the volume of interest with respect to the identified predetermined segmented structure</claim-text>
<claim-text>wherein the MRSI system (100) further comprises a MRS analyzer (128) configured to determine a biochemical composition of the volume of interest (VOI) positioned in the segmented structure.</claim-text></claim-text></claim>
<claim id="c-en-01-0002" num="0002">
<claim-text>The MRSI system (100) of claim 1, wherein the predetermined segmented structure is represented as a mesh, and the volume of interest generator (208) is configured to position the volume of interest with respect to the predetermined segmented structure using mesh vertices as anchors.</claim-text></claim>
<claim id="c-en-01-0003" num="0003">
<claim-text>The MRSI system (100) of any of claims 1 to 2, wherein the volume of interest is positioned completely inside of the predetermined segmented structure; or<br/>
wherein the volume of interest is positioned partially inside and partially outside of the predetermined segmented structure; or<br/>
wherein the volume of interest is positioned completely outside of the predetermined segmented structure.</claim-text></claim>
<claim id="c-en-01-0004" num="0004">
<claim-text>The MRSI system (100) of claim 3, wherein the volume of interest generator (208) is configured to position the volume of interest at a first location with respect to the<!-- EPO <DP n="12"> --> predetermined segmented structure in first image data and at a second location with respect to the predetermined segmented structure in second image data, wherein the first and second location are substantially the same location.</claim-text></claim>
<claim id="c-en-01-0005" num="0005">
<claim-text>The MRSI system (100) of any of claims 1 to 4, wherein the volume of interest generator (208) is configured to position the volume of interest based at least on one or more previously positioned volumes of interest.</claim-text></claim>
<claim id="c-en-01-0006" num="0006">
<claim-text>The MRSI system (100) of any of claims 1 to 5, wherein the volume of interest includes one or more voxels.</claim-text></claim>
<claim id="c-en-01-0007" num="0007">
<claim-text>The MRSI system (100) of any of claims 1 to 6, wherein the biochemical composition is indicative of a neurodegenerative disorder of a patient corresponding to the MRI image data.</claim-text></claim>
<claim id="c-en-01-0008" num="0008">
<claim-text>A method, comprising:
<claim-text>identifying (904) a predetermined segmented structure in segmented MRI image data; and</claim-text>
<claim-text>positioning (906) a volume of interest (VOI) with respect to the identified predetermined segmented structure for a Magnetic Resonance Spectroscopic (MRS) biochemical composition analysis, wherein the positioning (906) is based on one or more rules for positioning the volume of interest (VOI) in the identified predetermined segmented structure, wherein the rules for positioning the volume of interest (VOI) are stored in a positioning rules bank; and</claim-text>
<claim-text>determining a biochemical composition of the volume of interest (VOI) positioned in the segmented structure.</claim-text></claim-text></claim>
<claim id="c-en-01-0009" num="0009">
<claim-text>The method of claim 8, wherein the predetermined segmented structure is represented as a mesh, and the positioning (906) includes positioning the volume of interest with respect to the predetermined segmented structure using mesh vertices as anchors.</claim-text></claim>
<claim id="c-en-01-0010" num="0010">
<claim-text>The method of any of claims 8 to 9, further comprising:<br/>
generating a database of reference data by processing MRI image data corresponding to patients with known neurodegenerative disorders and patients with no<!-- EPO <DP n="13"> --> neurodegenerative disorders and storing the biochemical compositions and a mapping between the biochemical compositions and the neurodegenerative disorders.</claim-text></claim>
<claim id="c-en-01-0011" num="0011">
<claim-text>The method of any of claims 8 to 10, further comprising:<br/>
determining a biochemical biomarker by processing MRI image data corresponding to patients with a known neurodegenerative disorder, wherein the biochemical composition provides a signature biochemical biomarker of the known neurodegenerative disorder.</claim-text></claim>
<claim id="c-en-01-0012" num="0012">
<claim-text>The method of any of claims 8 to 11, further comprising:<br/>
positioning the volume of interest with respect to the identified predetermined segmented structure of second MRI image data based on the one or more of the rules for positioning, wherein the volume of interest in the MRI image data and in the second MRI image data are positioned at the same location.</claim-text></claim>
<claim id="c-en-01-0013" num="0013">
<claim-text>The method of claim 12, wherein the MRI image data and the second MRI image data correspond to a same patient; or wherein the MRI image data and the second MRI image data correspond to different patients.</claim-text></claim>
<claim id="c-en-01-0014" num="0014">
<claim-text>A computer readable storage medium comprising instructions for causing a processor system to carry out the method according to any one of claims 8-13.</claim-text></claim>
</claims>
<claims id="claims02" lang="de"><!-- EPO <DP n="14"> -->
<claim id="c-de-01-0001" num="0001">
<claim-text>System (100) zur Magnetresonanzspektroskopie-Bildgebung (MRS-B), das aus Folgendem besteht:
<claim-text>einer Strukturkennung (206), die so konfiguriert ist, dass sie eine vorgegebene segmentierte Struktur in segmentierten MRI-Bilddaten identifiziert;</claim-text>
<claim-text>eine Positionierungsregel-Datenbank (210), die so konfiguriert ist, dass sie Regeln für die Positionierung eines interessierenden Volumens (IV) in Bezug auf die identifizierte vorbestimmte segmentierte Struktur der segmentierten MRI-Bilddaten für eine Analyse der biochemischen Zusammensetzung mittels Magnetresonanzspektroskopie (MRS) speichert; und</claim-text>
<claim-text>einen Generator (208) für interessierende Volumen, der so konfiguriert ist, dass er das interessierende Volumen in Bezug auf die identifizierte vorbestimmte segmentierte Struktur auf Grundlage einer oder mehrerer Regeln zur Positionierung des interessierenden Volumens in Bezug auf die identifizierte vorbestimmte segmentierte Struktur positioniert</claim-text>
<claim-text>wobei das MRS-B-System (100) ferner einen MRS-Analysator (128) umfasst, der so konfiguriert ist, dass er eine biochemische Zusammensetzung des in der segmentierten Struktur positionierten Volumens von<!-- EPO <DP n="15"> --> Interesse (IV) bestimmt.</claim-text></claim-text></claim>
<claim id="c-de-01-0002" num="0002">
<claim-text>MRS-B-System (100) nach Anspruch 1, bei dem die vorgegebene segmentierte Struktur als ein Netz dargestellt wird und der Generator (208) für interessierende Volumen so konfiguriert ist, dass er das interessierende Volumen in Bezug auf die vorgegebene segmentierte Struktur unter Verwendung von Netz-Eckpunkten als Verankerungspunkte positioniert.</claim-text></claim>
<claim id="c-de-01-0003" num="0003">
<claim-text>Das MRS-B-System (100) nach einem der Ansprüche 1 bis 2, wobei das interessierende Volumen vollständig innerhalb der vorgegebenen segmentierten Struktur positioniert ist; oder<br/>
wobei das interessierende Volumen teilweise innerhalb und teilweise außerhalb der vorbestimmten segmentierten Struktur positioniert ist; oder<br/>
wobei das interessierende Volumen vollständig außerhalb der vorgegebenen segmentierten Struktur positioniert ist.</claim-text></claim>
<claim id="c-de-01-0004" num="0004">
<claim-text>MRS-B-System (100) nach Anspruch 3, wobei der Generator (208) für interessierende Volumen so konfiguriert ist, dass er das interessierende Volumen an einer ersten Stelle in Bezug auf die vorbestimmte segmentierte Struktur in ersten Bilddaten und an einer zweiten Stelle in Bezug auf die vorbestimmte segmentierte Struktur in zweiten Bilddaten positioniert,<!-- EPO <DP n="16"> --> wobei die erste und die zweite Stelle im Wesentlichen die gleiche Stelle sind.</claim-text></claim>
<claim id="c-de-01-0005" num="0005">
<claim-text>MRS-B-System (100) nach einem der Ansprüche 1 bis 4, wobei der Generator (208) des interessierenden Volumen-so konfiguriert ist, dass er das interessierende Volumen auf Grundlage mindestens eines oder mehrerer zuvor positionierter interessierender Volumina positioniert.</claim-text></claim>
<claim id="c-de-01-0006" num="0006">
<claim-text>MRS-B-System (100) nach einem der Ansprüche 1 bis 5, wobei das interessierende Volumen einen oder mehrere Voxel einschließt.</claim-text></claim>
<claim id="c-de-01-0007" num="0007">
<claim-text>MRS-B-System (100) nach einem der Ansprüche 1 bis 6, wobei die biochemische Zusammensetzung auf eine neurodegenerative Erkrankung eines Patienten gemäß den MRI-Bilddaten hinweist.</claim-text></claim>
<claim id="c-de-01-0008" num="0008">
<claim-text>Verfahren, die aus Folgendem besteht:
<claim-text>Identifizierung (904) einer vorbestimmten segmentierten Struktur in segmentierten MRI-Bilddaten; und</claim-text>
<claim-text>Positionierung (906) eines interessierenden Volumens (IV) in Bezug auf die identifizierte vorbestimmte segmentierte Struktur für eine Analyse der biochemischen Zusammensetzung mittels Magnetresonanzspektroskopie (MRS), wobei die Positionierung (906) auf einer oder mehreren Regeln zur Positionierung des interessierenden Volumens (IV) in der identifizierten<!-- EPO <DP n="17"> --> vorbestimmten segmentierten Struktur basiert, wobei die Regeln zur Positionierung des interessierenden Volumens (IV) in einer Positionierungsregel-Datenbank gespeichert sind; und</claim-text>
<claim-text>Bestimmung einer biochemischen Zusammensetzung des in der segmentierten Struktur positionierten interessierenden Volumens (IV).</claim-text></claim-text></claim>
<claim id="c-de-01-0009" num="0009">
<claim-text>Verfahren nach Anspruch 8, bei dem die vorgegebene segmentierte Struktur als ein Netz dargestellt wird und die Positionierung (906) die Positionierung des interessierenden Volumens in Bezug auf die vorgegebene segmentierte Struktur unter Verwendung von Netz-Eckpunkten als Verankerungspunkte umfasst.</claim-text></claim>
<claim id="c-de-01-0010" num="0010">
<claim-text>Verfahren nach einem der Ansprüche 8 bis 9, das ferner Folgendes umfasst:<br/>
Erzeugung einer Datenbank mit Referenzdaten durch Verarbeitung von MRI-Bilddaten, die Patienten mit bekannten neurodegenerativen Störungen und Patienten ohne neurodegenerative Störungen zugeordnet sind, und Speicherung der biochemischen Zusammensetzungen und einer Zuordnung zwischen den biochemischen Zusammensetzungen und den neurodegenerativen Erkrankungen.</claim-text></claim>
<claim id="c-de-01-0011" num="0011">
<claim-text>Verfahren nach einem der Ansprüche 8 bis 10, das ferner Folgendes umfasst:<br/>
Bestimmung eines biochemischen Biomarkers durch Verarbeitung<!-- EPO <DP n="18"> --> von MRI-Bilddaten, die Patienten mit einer bekannten neurodegenerativen Erkrankung zugeordnet sind, wobei die biochemische Zusammensetzung einen charakteristischen biochemischen Biomarker der bekannten neurodegenerativen Erkrankung darstellt.</claim-text></claim>
<claim id="c-de-01-0012" num="0012">
<claim-text>Verfahren nach einem der Ansprüche 8 bis 11, das ferner Folgendes umfasst:<br/>
Positionierung des interessierenden Volumens in Bezug auf die identifizierte vorbestimmte segmentierte Struktur von zweiten MRI-Bilddaten auf Grundlage einer oder mehrerer der Positionierungsregeln, wobei das interessierende Volumen in den MRI-Bilddaten und in den zweiten MRI-Bilddaten an derselben Stelle positioniert wird.</claim-text></claim>
<claim id="c-de-01-0013" num="0013">
<claim-text>Verfahren nach Anspruch 12, wobei die MRI-Bilddaten und die zweiten MRI-Bilddaten einem gleichen Patienten zugeordnet sind; oder wobei die MRI-Bilddaten und die zweiten MRI-Bilddaten verschiedenen Patienten zugeordnet sind.</claim-text></claim>
<claim id="c-de-01-0014" num="0014">
<claim-text>Computerlesbares Speichermedium mit Anweisungen, um ein Prozessor-System zu veranlassen, das Verfahren gemäß einem der Ansprüche 8 bis 13 auszuführen.</claim-text></claim>
</claims>
<claims id="claims03" lang="fr"><!-- EPO <DP n="19"> -->
<claim id="c-fr-01-0001" num="0001">
<claim-text>Système d'imagerie spectroscopique par résonance magnétique (ISRM) (100), comprenant:
<claim-text>un identifiant de structure (206), lequel est configuré pour identifier une structure segmentée prédéterminée dans des données d'image IRM segmentées;</claim-text>
<claim-text>une banque de règles de positionnement (210), laquelle est configurée pour mémoriser des règles pour le positionnement d'un volume d'intérêt (VOI) par rapport à la structure segmentée prédéterminée identifiée des données d'image IRM segmentées pour une analyse de composition biochimique par spectroscopie par résonance magnétique (SRM); et</claim-text>
<claim-text>un générateur de volume d'intérêt (208), lequel est configuré pour positionner le volume d'intérêt par rapport à la structure segmentée prédéterminée identifiée en fonction d'au moins une règle pour le positionnement du volume d'intérêt par rapport à la structure segmentée prédéterminée identifiée,</claim-text>
<claim-text>dans lequel le système ISRM (100) comprend en outre un analyseur SRM (128) configuré pour déterminer une composition biochimique du volume d'intérêt (VOI) positionné dans la structure segmentée.</claim-text></claim-text></claim>
<claim id="c-fr-01-0002" num="0002">
<claim-text>Système ISRM (100) selon la revendication 1, dans<!-- EPO <DP n="20"> --> lequel la structure segmentée prédéterminée est représentée en tant qu'un maillage, et le générateur de volume d'intérêt (208) est configuré pour positionner le volume d'intérêt par rapport à la structure segmentée prédéterminée en utilisant des sommets de maillage en tant que moyens d'ancrage.</claim-text></claim>
<claim id="c-fr-01-0003" num="0003">
<claim-text>Système ISRM (100) selon l'une quelconque des revendications 1 à 2, dans lequel le volume d'intérêt est positionné complètement à l'intérieur de la structure segmentée prédéterminée; ou<br/>
dans lequel le volume d'intérêt est positionné partiellement à l'intérieur et partiellement à l'extérieur de la structure segmentée prédéterminée; ou<br/>
dans lequel le volume d'intérêt est positionné complètement à l'extérieur de la structure segmentée prédéterminée.</claim-text></claim>
<claim id="c-fr-01-0004" num="0004">
<claim-text>Système ISRM (100) selon la revendication 3, dans lequel le générateur de volume d'intérêt (208) est configuré pour positionner le volume d'intérêt à un premier emplacement par rapport à la structure segmentée prédéterminée dans les premières données d'image et à un second emplacement par rapport à la structure segmentée prédéterminée dans les secondes données d'image,<br/>
<!-- EPO <DP n="21"> -->dans lequel le premier et le second emplacement sont sensiblement le même emplacement.</claim-text></claim>
<claim id="c-fr-01-0005" num="0005">
<claim-text>Système ISRM (100) selon l'une quelconque des revendications 1 à 4, dans lequel le générateur de volume d'intérêt (208) est configuré pour positionner le volume d'intérêt en fonction d'au moins un volume d'intérêt précédemment positionné.</claim-text></claim>
<claim id="c-fr-01-0006" num="0006">
<claim-text>Système ISRM (100) selon l'une quelconque des revendications 1 à 5, dans lequel le volume d'intérêt comprend au moins un voxel.</claim-text></claim>
<claim id="c-fr-01-0007" num="0007">
<claim-text>Système ISRM (100) selon l'une quelconque des revendications 1 à 6, dans lequel la composition biochimique indique un trouble neurodégénératif d'un sujet correspondant aux données d'image IRM.</claim-text></claim>
<claim id="c-fr-01-0008" num="0008">
<claim-text>Procédé, consistant:
<claim-text>à identifier (904) une structure segmentée prédéterminée dans des données d'image IRM segmentées; et</claim-text>
<claim-text>à positionner (906) un volume d'intérêt (VOI) par rapport à la structure segmentée prédéterminée identifiée pour une analyse de composition biochimique par spectroscopie par résonance magnétique (SRM), dans lequel le positionnement (906) est basé sur au moins une règle pour le positionnement du volume d'intérêt (VOI) dans la structure segmentée prédéterminée identifiée, dans lequel les règles de positionnement<!-- EPO <DP n="22"> --> du volume d'intérêt (VOI) sont mémorisées dans une banque de règles de positionnement; et</claim-text>
<claim-text>à déterminer une composition biochimique du volume d'intérêt (VOI) positionné dans la structure segmentée.</claim-text></claim-text></claim>
<claim id="c-fr-01-0009" num="0009">
<claim-text>Procédé selon la revendication 8, dans lequel la structure segmentée prédéterminée est représentée en tant qu'un maillage, et le positionnement (906) comprend le positionnement du volume d'intérêt par rapport à la structure segmentée prédéterminée en utilisant des sommets de maillage en tant que moyens d'ancrage.</claim-text></claim>
<claim id="c-fr-01-0010" num="0010">
<claim-text>Procédé selon l'une quelconque des revendications 8 à 9, consistant en outre:<br/>
à générer une base de données des données de référence en traitant les données d'image IRM correspondant aux sujets souffrant de troubles neurodégénératifs connus et aux sujets sans troubles neurodégénératifs et en mémorisant les compositions biochimiques et une cartographie entre les compositions biochimiques et les troubles neurodégénératifs.</claim-text></claim>
<claim id="c-fr-01-0011" num="0011">
<claim-text>Procédé selon l'une quelconque des revendications 8 à 10, consistant en outre:<br/>
à déterminer un biomarqueur biochimique en traitant les données d'image IRM correspondant à des sujets<!-- EPO <DP n="23"> --> atteints d'un trouble neurodégénératif connu, dans lequel la composition biochimique fournit un biomarqueur biochimique signature du trouble neurodégénératif connu.</claim-text></claim>
<claim id="c-fr-01-0012" num="0012">
<claim-text>Procédé selon l'une quelconque des revendications 8 à 11, consistant en outre:<br/>
à positionner le volume d'intérêt par rapport à la structure segmentée prédéterminée identifiée des secondes données d'image IRM en fonction d'au moins une règle pour le positionnement, dans lequel le volume d'intérêt dans les données d'image IRM et dans les secondes données d'image IRM est positionné à au même endroit.</claim-text></claim>
<claim id="c-fr-01-0013" num="0013">
<claim-text>Procédé selon la revendication 12, dans lequel les données d'image IRM et les secondes données d'image IRM correspondent à un même sujet; ou dans lequel les données d'image IRM et les secondes données d'image IRM correspondent à différents sujets.</claim-text></claim>
<claim id="c-fr-01-0014" num="0014">
<claim-text>Support de stockage lisible par ordinateur comprenant des instructions permettant d'amener un système de processeur à mettre en œuvre le procédé selon l'une quelconque des revendications 8-13.</claim-text></claim>
</claims>
<drawings id="draw" lang="en"><!-- EPO <DP n="24"> -->
<figure id="f0001" num="1"><img id="if0001" file="imgf0001.tif" wi="141" he="215" img-content="drawing" img-format="tif"/></figure><!-- EPO <DP n="25"> -->
<figure id="f0002" num="2,3"><img id="if0002" file="imgf0002.tif" wi="139" he="204" img-content="drawing" img-format="tif"/></figure><!-- EPO <DP n="26"> -->
<figure id="f0003" num="4,5"><img id="if0003" file="imgf0003.tif" wi="75" he="187" img-content="drawing" img-format="tif"/></figure><!-- EPO <DP n="27"> -->
<figure id="f0004" num="6,7"><img id="if0004" file="imgf0004.tif" wi="139" he="221" img-content="drawing" img-format="tif"/></figure><!-- EPO <DP n="28"> -->
<figure id="f0005" num="8,9"><img id="if0005" file="imgf0005.tif" wi="131" he="213" img-content="drawing" img-format="tif"/></figure>
</drawings>
<ep-reference-list id="ref-list">
<heading id="ref-h0001"><b>REFERENCES CITED IN THE DESCRIPTION</b></heading>
<p id="ref-p0001" num=""><i>This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.</i></p>
<heading id="ref-h0002"><b>Non-patent literature cited in the description</b></heading>
<p id="ref-p0002" num="">
<ul id="ref-ul0001" list-style="bullet">
<li><nplcit id="ref-ncit0001" npl-type="s"><article><author><name>RAKESH SHARMA</name></author><atl>Molecular Imaging by Proton Magnetic Resonance Imaging (MRI) and MR Spectroscopic Imaging (MRSI) in Neurodegeneration</atl><serial><sertitle>INFORMATICA MEDICA SLOVENICA</sertitle><pubdate><sdate>20050630</sdate><edate/></pubdate><vid>10</vid><ino>1</ino></serial><location><pp><ppf>35</ppf><ppl>55</ppl></pp></location></article></nplcit><crossref idref="ncit0001">[0006]</crossref></li>
<li><nplcit id="ref-ncit0002" npl-type="b"><article><atl>Manual annotation, 3-D shape reconstruction, and traumatic brain injury analysis</atl><book><author><name>L.ZAGORCHEV</name></author><author><name>A. GOSHTASBY</name></author><author><name>K. PAULSEN</name></author><author><name>T. MCALLISTER</name></author><author><name>S. YOUNG</name></author><author><name>J. WEESE</name></author><book-title>Int'l Workshop Multimodal Brain Image Analysis (MBIA)</book-title><imprint><name/><pubdate>20110900</pubdate></imprint></book></article></nplcit><crossref idref="ncit0002">[0021]</crossref></li>
<li><nplcit id="ref-ncit0003" npl-type="s"><article><author><name>L.ZAGORCHEV</name></author><author><name>C. MEYER</name></author><author><name>T.STEHLE</name></author><author><name>R.KNESER</name></author><author><name>S. YOUNG</name></author><author><name>J. WEESE</name></author><atl>Evaluation of Traumatic Brain Injury patients using a shape-constrained deformable model</atl><serial><sertitle>Int'l Workshop Multimodal Brain Image Analysis (MBIA)</sertitle><pubdate><sdate>20110900</sdate><edate/></pubdate></serial></article></nplcit><crossref idref="ncit0003">[0021]</crossref></li>
</ul></p>
</ep-reference-list>
</ep-patent-document>
